7NSO

Structure of ErmDL-Erythromycin-stalled 70S E. coli ribosomal complex with P-tRNA

これはPDB形式変換不可エントリーです。

7NSO の概要

• エントリーDOI: 10.2210/pdb7nso/pdb
• EMDBエントリー: 12573
• 分子名称: 23S rRNA (2903-MER), 50S ribosomal protein L14, 50S ribosomal protein L15, ... (56 entities in total)
• 機能のキーワード: antibiotic, ermdl, erythromycin, macrolide, stalling, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 55
• 化学式量合計: 2143698.54

構造登録者

Beckert, B.,Wilson, D.N. (登録日: 2021-03-08, 公開日: 2021-07-14, 最終更新日: 2024-11-06)

主引用文献

Beckert, B.,Leroy, E.C.,Sothiselvam, S.,Bock, L.V.,Svetlov, M.S.,Graf, M.,Arenz, S.,Abdelshahid, M.,Seip, B.,Grubmuller, H.,Mankin, A.S.,Innis, C.A.,Vazquez-Laslop, N.,Wilson, D.N.
Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics.
Nat Commun, 12:4466-4466, 2021

PubMed Abstract: Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics.

PubMed: 34294725
DOI: 10.1038/s41467-021-24674-9

実験手法

ELECTRON MICROSCOPY (2.9 Å)